title: The relationship between DNA adduct formation by benzo[a]pyrene and expression of its activation enzyme cytochrome P450 1A1 in rat.
abstract: Benzo[a]pyrene (BaP) is a human carcinogen requiring metabolic activation prior to reaction with DNA. Cytochrome P450 (CYP) 1A1 is the most important hepatic and intestinal enzyme in both BaP activation and detoxification. CYP1A2 is also capable of oxidizing BaP, but to a lesser extent. The induction of CYP1A1/2 by BaP and/or β-naphthoflavone in liver and small intestine of rats was investigated. Both BaP and β-naphthoflavone induced CYP1A expression and increased enzyme activities in both organs. Moreover, the induction of CYP1A enzyme activities resulted in an increase in formation of BaP-DNA adducts detected by (32)P-postlabeling in rat liver and in the distal part of small intestine in vivo. The increases in CYP1A enzyme activity were also associated with bioactivation of BaP and elevated BaP-DNA adduct levels in ex vivo incubations of microsomes of both organs with DNA and BaP. These findings indicate a stimulating effect of both compounds on BaP-induced carcinogenesis.
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Hodek
authors.forename: Jitka
authors.initials: J
authors.lastname: Koblihová
authors.forename: René
authors.initials: R
authors.lastname: Kizek
authors.forename: Eva
authors.initials: E
authors.lastname: Frei
authors.forename: Volker M
authors.initials: VM
authors.lastname: Arlt
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborová
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D002855:Chromatography, Thin Layer; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics; D018736:DNA Adducts / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D018736:DNA Adducts; D004785:Environmental Pollutants; D007527:Isoenzymes; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2
keywords: (32)P-postlabeling; 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; 5-bromo-4-chloro-3′-indolyphosphate p-toluidine salt; 7-ethoxyresorufin O-deethylation; 7-methoxyresorufin O-deethylation; AHR; BCIP; BNF; BPDE; BaP; BaP-7,8-dihydrodiol-9,10-epoxide; Benzo[a]pyrene; CYP; Cytochrome P450 1A1/2; DMSO; DNA adducts; EROD; Induction; MROD; Metabolic Activation and Detoxification; NBT; PAH; RAL; SDS; TLC; aryl hydrocarbon receptor; benzo[a]pyrene; cytochrome P450; dG-N(2)-BPDE; dimethyl sulfoxide; mEH; microsomal epoxide hydrolase; nitro-blue tetrazolium chloride; polycyclic aromatic hydrocarbon; relative adduct labeling; sodium dodecyl sulfate; thin-layer chromatography; β-naphthoflavone